Randomized placebo controlled human volunteer trial of a live oral cholera vaccine VA1.3 for safety and immune response

Mahalanabis, Dilip; Ramamurthy, Thandavarayan; Nair, G. Balakrish; Ghosh, Amit; Shaikh, Saijuddin; Sen, Bandana; Thungapathra, M.; Ghosh, Ram Krishna; Pazhani, Gururaja P.; Nandy, Ranjan K.; Jana, Snehasis; Bhattacharya, Sujit

doi:10.1016/j.vaccine.2009.05.065

Cited by 29 publications

(14 citation statements)

References 29 publications

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“…(b) Similar rise in vibriocidal antibody titre [4] as after VA 1.3 was necessary for going into a field trial (same or above the lower 95% confidence interval i.e. 49%).…”

Section: Methodsmentioning

confidence: 91%

“…In the removable intestinal tie-adult rabbit diarrhea model (RITARD) model this strain was found to be non-reactogenic and provided full protection against the challenge doses of both V. cholerae O1, classical and El Tor. In a large human volunteer study with live oral cholera vaccine VA1.3 we have shown that seroconversion rate with this novel vaccine is excellent and the adverse effects are negligible [4]. Further, the vaccine strain was not excreted in the stool.…”

Section: Introductionmentioning

confidence: 87%

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Safety and Immunogenicity of a Live Oral Recombinant Cholera Vaccine VA1.4: A Randomized, Placebo Controlled Trial in Healthy Adults in a Cholera Endemic Area in Kolkata, India

et al. 2014

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BackgroundA live oral cholera vaccine VA 1.4 developed from a non-toxigenic Vibrio cholerae O1 El Tor strain using ctxB gene insertion was further developed into a clinical product following cGMP and was evaluated in a double-blind randomized placebo controlled parallel group two arm trial with allocation ratio of 1∶1 for safety and immunogenicity in men and women aged 18–60 years from Kolkata, India.MethodA lyophilized dose of 1.9×109 CFU (n = 44) or a placebo (n = 43) reconstituted with a diluent was administered within 5 minutes of drinking 100 ml of a buffer solution made of sodium bicarbonate and ascorbic acid and a second dose on day 14.ResultThe vaccine did not elicit any diarrhea related adverse events. Other adverse events were rare, mild and similar in two groups. One subject in the vaccine group excreted the vaccine strain on the second day after first dose. The proportion of participants who seroconverted (i.e. had 4-folds or higher rise in reciprocal titre) in the vaccine group were 65.9% (95% CI: 50.1%–79.5%) at both 7 days (i.e. after 1st dose) and 21 days (i.e. after 2nd dose). None of the placebo recipients seroconverted. Anti-cholera toxin antibody was detected in very few recipients of the vaccine.ConclusionThis study demonstrates that VA 1.4 at a single dose of 1.9×109 is safe and immunogenic in adults from a cholera endemic region. No additional benefit after two doses was seen.Trial RegistrationClinical Trials Registry-India, National Institute of Medical Statistics (Indian Council of Medical Research) CTRI/2012/04/002582

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“…(b) Similar rise in vibriocidal antibody titre [4] as after VA 1.3 was necessary for going into a field trial (same or above the lower 95% confidence interval i.e. 49%).…”

Section: Methodsmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 87%

Safety and Immunogenicity of a Live Oral Recombinant Cholera Vaccine VA1.4: A Randomized, Placebo Controlled Trial in Healthy Adults in a Cholera Endemic Area in Kolkata, India

et al. 2014

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“…Live attenuated vaccines against a number of enteric bacterial diseases have been successfully developed (Vivotif for typhoid fever and Orochol for cholera), with other candidates being in various stages of clinical development (17,18,28,44). Previously, attenuated ETEC strains expressing different colonization factors have been produced and tested in phase I trials at maximum doses of 2 ϫ 10 10 CFU (10,40).…”

Section: Discussionmentioning

confidence: 99%

“…Other exclusion criteria included immunoglobulin A deficiency; alcohol or drug VOL. 18,2011 ACE527 ETEC VACCINE 2119 dependence within the preceding 3 years; vaccination or receipt of an investigational product in the preceding month; employment as a food handler, child care provider, or health care worker; having household contacts who were immunocompromised, Ͻ2 years old, or Ͼ80 years old; abnormal hematology/serum chemistry; positive screen for HIV or hepatitis virus B/C; having abnormal stool patterns (less than 3 per week or more than 3 per day); history of diarrhea in the 7 days prior to vaccination; regular use of laxatives or antacids; history of vaccination against or ingestion of ETEC, cholera toxin, or LT within 3 years; symptoms consistent with traveler's diarrhea concurrent with travel to countries where ETEC is endemic within 2 years; and known allergy to quinolones, trimethoprim-sulfamethoxazole, or penicillins. Each participant signed an informed-consent form and was required to score Ն70% on a study comprehension assessment prior to undergoing study-specific procedures.…”

Section: Methodsmentioning

confidence: 99%

A Combination Vaccine Consisting of Three Live Attenuated Enterotoxigenic Escherichia coli Strains Expressing a Range of Colonization Factors and Heat-Labile Toxin Subunit B Is Well Tolerated and Immunogenic in a Placebo-Controlled Double-Blind Phase I Trial in Healthy Adults

Harro

Sack

Bourgeois

et al. 2011

Clin Vaccine Immunol

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Immune responses against colonization factors (CFs) and the nontoxic B component of the enterotoxigenicEscherichia coli (ETEC) heat-labile toxin (LTB) are considered to be important for immunity against diarrhea caused by ETEC. Individual live attenuated ETEC derivatives that have had their toxin genes removed and whose aroC, ompC, and ompF genes are deleted have shown promise as vaccines against ETEC. The development of such strains has culminated in the testing of a three-strain-combination live attenuated vaccine known as ACE527, comprised of strains ACAM2025 expressing colonization factor antigen I (CFA/I) and LTB; ACAM2022, expressing CS5, CS6, and LTB; and ACAM2027, expressing CS1, CS2, CS3, and LTB. The recombinant CF and LTB genes expressed in the three strains were inserted into the bacterial chromosome to ensure their stable inheritance and expression without the requirement for any selection. ACE527 has been tested in a randomized placebo-controlled, double-blind, phase I safety and immunogenicity study in healthy adult volunteers and proved to be well tolerated and immunogenic at dose levels of 10 10 and 10 11 total CFU. There was no indication of strain interference on the basis of fecal shedding patterns, with all three being detected in the feces of 50% and 83% of low-and high-dose vaccine recipients, respectively. Similarly, strong immune responses to LTB and to CFs expressed on all three constituent strains were induced, with at least 50% of subjects in the high-dose group responding to LTB, CFA/I, CS3, and CS6.

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“…Other live oral vaccine strains that have been found to be well tolerated and immunogenic in humans are V. cholerae 638 (12), and CTBexpressing strain VA1.3 (28). Both are attenuated EL Tor deriva-tives; strain 638 protected adult volunteers in a challenge study (12).…”

mentioning

confidence: 99%

Insights from Natural Infection-Derived Immunity to Cholera Instruct Vaccine Efforts

Pasetti¹,

Levine²

2012

Clin. Vaccine Immunol.

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Randomized placebo controlled human volunteer trial of a live oral cholera vaccine VA1.3 for safety and immune response

Cited by 29 publications

References 29 publications

Safety and Immunogenicity of a Live Oral Recombinant Cholera Vaccine VA1.4: A Randomized, Placebo Controlled Trial in Healthy Adults in a Cholera Endemic Area in Kolkata, India

Safety and Immunogenicity of a Live Oral Recombinant Cholera Vaccine VA1.4: A Randomized, Placebo Controlled Trial in Healthy Adults in a Cholera Endemic Area in Kolkata, India

A Combination Vaccine Consisting of Three Live Attenuated Enterotoxigenic Escherichia coli Strains Expressing a Range of Colonization Factors and Heat-Labile Toxin Subunit B Is Well Tolerated and Immunogenic in a Placebo-Controlled Double-Blind Phase I Trial in Healthy Adults

Insights from Natural Infection-Derived Immunity to Cholera Instruct Vaccine Efforts

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